Belinostat, Carboplatin and Paclitaxel (BelCaP) Compared to Carboplatin and Paclitaxel in Patients With Cancer of Unknown Primary

This study has been completed.
Sponsor:
Collaborator:
Spectrum Pharmaceuticals, Inc
Information provided by (Responsible Party):
Onxeo
ClinicalTrials.gov Identifier:
NCT00873119
First received: March 31, 2009
Last updated: July 7, 2015
Last verified: July 2015
  Purpose

The purpose of this study is to assess efficacy and safety of belinostat in combination with carboplatin and paclitaxel in patients with previously untreated carcinoma of unknown primary.


Condition Intervention Phase
Carcinoma of Unknown Primary
Drug: belinostat, carboplatin, paclitaxel
Drug: carboplatin, paclitaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label Randomized Phase II Trial of Belinostat (PXD101) in Combination With Carboplatin and Paclitaxel (BelCaP) Compared to Carboplatin and Paclitaxel in Patients With Previously Untreated Carcinoma of Unknown Primary

Resource links provided by NLM:


Further study details as provided by Onxeo:

Primary Outcome Measures:
  • Progression Free Survival [ Time Frame: Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study ] [ Designated as safety issue: No ]
    Time from the date of randomization to the time of disease progression or death due to any cause, measured by RECIST criteria (Response Evaluation Criteria In Solid Tumors).


Secondary Outcome Measures:
  • Best Overall Response [ Time Frame: Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study ] [ Designated as safety issue: No ]
    The best overall response in an individual patient according to the RECIST criteria (Eisenhauer 2009 ) is the best response recorded from the start of the treatment until disease progression/recurrence. Objective response is defined as best overall response of complete response (CR) or partial response (PR)

  • Overall Survival (OS) [ Time Frame: Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study ] [ Designated as safety issue: No ]
    Time from the date of randomization to the date of death

  • Time to Response [ Time Frame: Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study ] [ Designated as safety issue: No ]
    For patients with overall best response being CR or PR, time to response was measured as the time from randomization to the first time when the measurement criteria for CR or PR (whichever status is recorded first) were met

  • Duration of Response [ Time Frame: Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study ] [ Designated as safety issue: No ]
    Duration of overall response was measured from the time that measurement criteria were first met for CR or PR (whichever status was recorded first) until the first date that PD ([Progressive Disease]) or death was documented

  • Time to Progression (TTP) [ Time Frame: Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study ] [ Designated as safety issue: No ]
    Time from the date of randomization to the time of disease progression


Enrollment: 89
Study Start Date: February 2009
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A - BelCaP
Group A: belinostat 1000 mg/m² administered as a 30 minute IV infusion once daily on days 1, 2 and 3, with at least 18 hours between infusions, followed by belinostat 2000 mg administered orally once daily on days 4 and 5, every 3-weeks, in combination with paclitaxel 175 mg/m² administered as an IV infusion following the infusion of belinostat on cycle day 3, and carboplatin (AUC 6) administered as a 30-60 minute IV infusion directly after the paclitaxel administration on cycle day 3.
Drug: belinostat, carboplatin, paclitaxel
Other Names:
  • PXD101, Belinostat
  • Carboplatin
  • Paclitaxel, Taxol
Active Comparator: Arm B - CaP
Group B: paclitaxel 175 mg/m² administered as an IV infusion directly followed by carboplatin (AUC 6) administered as a 30-60 minute IV infusion on cycle day 1 of a 3-weekly cycle.
Drug: carboplatin, paclitaxel
Other Names:
  • Carboplatin
  • Paclitaxel, Taxol

Detailed Description:

This is an open-label, multinational, multicenter, randomized, comparative efficacy and safety study in previously untreated patients with carcinoma of unknown primary. Patients meeting inclusion and exclusion criteria will be randomized to treatment in Arm A (BelCaP) or Arm B (CaP).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with CUP where the primary site had not been revealed by complete history, physical examination (including gynecological examination when appropriate), computed tomography (CT) scan of the chest, abdomen and pelvis, bilateral mammography (in women with adenocarcinoma or poorly differentiated carcinoma), routine laboratory studies (complete blood cell counts, electrolytes, urinalysis, liver and renal function tests), and directed work-up of any other symptomatic areas.
  • Light microscopic pathologic diagnosis of adenocarcinoma (including poorly differentiated), squamous cell carcinoma, or poorly differentiated carcinoma. Patients with poorly differentiated carcinoma must have immunohistochemical stains to confirm the diagnosis of carcinoma, and to rule out other tumor types. Note: patients with a light microscopic histology diagnosis of "poorly differentiated neoplasm, not otherwise classified" did not fulfill the criteria for inclusion, unless immunohistochemical staining confirmed the diagnosis of carcinoma.
  • Signed consent of an IRB ([Institutional Review Board])/IEC ([Independent ethics committee]) approved ICF ([Informed Consent Form]).
  • At least one measurable lesion according to RECIST ([response evaluation criteria in solid tumors ]) criteria. Note, target lesions could only be selected within previously irradiated areas if newly arising or clearly progressing after irradiation as proven by repeat scanning
  • Performance status Eastern Cooperative Oncology Group (ECOG) ≤ 2.
  • Age ≥ 18 years.
  • A negative serum or urine pregnancy test for women of childbearing potential. Postmenopausal women must have been amenorrheic for ≥ 12 months to be considered of non-childbearing potential.
  • Serum potassium within normal range.
  • Acceptable coagulation status: Prothrombin time/International normalized ratio PT/INR ([international normalized ratio]), and activated partial thromboplastin time (APTT) ≤ 1.5 × upper limit of normal (ULN) or in the therapeutic range if on anticoagulation therapy.
  • Acceptable liver, renal and bone marrow function including the following:

    1. Bilirubin ≤ 1.5 times ULN (if liver metastases were present, then ≤ 3 × ULN was allowed).
    2. Aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT), alanine amino transferase/serum glutamic pyruvic transaminase (ALT/SGPT), and alkaline phosphatase ≤ 3 times ULN (if liver metastases were present, then ≤ 5 × ULN was allowed).
    3. An estimated creatinine clearance ≥ 45 mL/min using an appropriate formula (Appendix C, protocol version 1.0, Appendix 16.1.1), or measured ethylenediaminetetraacetic acid (EDTA) renal clearance ≥ 45 mL/min.
    4. Absolute neutrophils count ≥ 1.5 × 109/L, platelets ≥ 100 × 109/L.
    5. Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/L (patients with chronic anemia due to underlying disease and its treatment could undergo blood transfusion prior to treatment in order to meet this criteria).

Exclusion Criteria:

  • Patients with well recognized subsets of CUP site where treatments directed towards a defined tumor type, or surgery, alternatively radiotherapy, can be advised:
  • Women with adenocarcinoma involving only axillary lymph nodes.
  • Women with papillary serous carcinoma of the peritoneum.
  • Women with adenocarcinoma with positive staining for estrogen receptor (ER) or progesterone receptor.
  • Young men (< 45 years) with poorly differentiated carcinoma consistent with an extragonadal germ cell tumor (carcinoma involving mediastinum or retroperitoneum, or elevated levels of beta-human chorionic gonadotropin or alpha-fetoprotein).
  • Men with bone metastases and/or adenocarcinoma, and abnormally elevated PSA ([Prostate specific antigen]) in their plasma.
  • Patients with squamous cell carcinoma involving only cervical lymph nodes, or inguinal lymph nodes.
  • Patients with neuroendocrine carcinomas determined according to standard pathology diagnosis procedures, including stains.
  • Patients with potentially completely resectable metastatic disease, or disease which can be adequately treated with radiotherapy only.
  • Patients with brain or meningeal metastases. Note, patients with adequately treated brain metastases, e.g. surgically resected, or adequately controlled by radiotherapy, with no residual neurological symptoms due to metastases and no steroid treatment required, could be enrolled. If clinical suspicion, adequate investigations should be performed to rule out brain metastases or meningeal involvement.
  • Prior systemic anti-tumor therapy, including chemotherapy administered in association to radiotherapy for sensitization, for CUP. Note, prior radiotherapy or surgery was allowed provided treatment was completed at least 4 weeks before randomization.
  • Treatment with investigational agents, including non-anti-tumor agents, within the last 4 weeks before randomization.
  • Co-existing active severe infection or any co-existing medical condition assessed by the Investigator as likely to interfere with study procedures.
  • Significant cardiovascular disease (New York Heart Association Class III or IV cardiac disease), myocardial infarction within the past 6 months, unstable angina, unstable arrhythmia or a need for anti-arrhythmic therapy (use of medication to control heart rate in patients with atrial fibrillation was allowed, if on stable medication for at least the last month prior to randomization and the medication not listed as causing Torsade de Points (Section 13.2, Appendix B, protocol version 1.0, Appendix 16.1.1), or evidence of acute ischemia on ECG.
  • Marked baseline prolongation of QT/QTc ([corrected QT interval]) interval, i.e., demonstration of a QTc interval > 450 millisecond (ms); Long QT Syndrome; the required use of concomitant medication that may cause Torsade de Pointes (Section 13.2, Appendix B, protocol version 1.0, Appendix 16.1.1).
  • Altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures.
  • History of a previous malignancy within 5 years with the exception of non-metastatic non-melanoma skin cancer or cervical carcinoma in situ. Prior systemic therapy for other malignancy completed at least 5 years before randomization is allowed.

Implemented with amendment 2 (study centers in France only): History of a previous malignancy, irrespective of time since diagnosis/treatment, with the exception of non metastatic non-melanoma skin cancer or cervical carcinoma in situ.

  • Known hypersensitivity to either platinum compounds or paclitaxel, or any components of the study medications, and inability for desensitization.
  • Known infection with HIV, or known active Hepatitis B or C infection.
  • Peripheral neuropathy ≥ Grade 2.
  • Pregnant or lactating females.
  • Women of childbearing age and potential who are not willing to use effective contraception during the study and until 30 days after last dose of study drug. Male patients or male patients who have female partners of childbearing age and potential who are not willing to use effective contraception during the study and until 30 days after last dose of study drug. Highly effective methods of birth control are defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intra uterine devices, sexual abstinence or vasectomized partner.
  • Patients that are not affiliated with social security (study centers in France only).
  • Implemented with amendment 1 (study centers in Denmark only): Hearing impairment assessed by the Investigator as being of such a degree that treatment with carboplatin cannot be initiated.
  • Implemented with amendment 1 (study centers in Denmark only): Bleeding tumors.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00873119

Locations
United States, Florida
Florida Cancer Specialists
Fort Myers, Florida, United States, 33619
United States, Georgia
Northwest Georgia Oncology Centers
Marietta, Georgia, United States, 30060
United States, Louisiana
Baton Rouge Medical Center
Baton Rouge, Louisiana, United States, 70809
United States, Maryland
Center for Cancers and Blood Disorders
Bethesda, Maryland, United States, 20817
United States, Missouri
Research Medical Center
Kansas City, Missouri, United States, 64132
United States, Ohio
Oncology Hematology Care Inc.
Cincinnati, Ohio, United States, 45242
United States, South Carolina
South Carolina Oncology Associates
Columbia, South Carolina, United States, 29210
United States, Tennessee
Chattanooga Oncology & Hematology Associates, PC
Chattanooga, Tennessee, United States, 37404
Tennessee Oncology Sarah Cannon Research
Nashville, Tennessee, United States, 37203
United States, Texas
South Texas Oncology and Hematology
San Antonio, Texas, United States, 78258
United States, Virginia
Virginia Cancer Institute
Richmond, Virginia, United States, 23230
Denmark
H:S Rigshospital, The Finsen Centre
Copenhagen, Denmark, DK-2100
France
CRLCC Francois Baclesse, Oncologie medicale
Caen, France, 14000
Centre Oscar Lambert
Lille, France, 59020
Centre Léon Bérard, Oncologie
Lyon, France, 69008
Centre Eugène Marquis
Rennes cedex, France, 35042
Centre Henri Becquerel, Oncologie Médicale
Rouen, France, 76038
Institut de Cancerologie de la Loire
Saint Priest en Jarez, France, 42270
Institut Gustave Roussy IGR
Villejuif cedex, France, 94805
Germany
Carl-Gustav-Carus Medicinische Klinik und Poliklinik I
Dresden, Germany, 01307
Kliniken Essen-Mitte
Essen, Germany, 45136
ASKLEPIOS Klinik Altona
Hamburg, Germany, 22763
Ostholstein-Onkologie
Oldenburg in Holstein, Germany, 23758
Sponsors and Collaborators
Onxeo
Spectrum Pharmaceuticals, Inc
Investigators
Study Director: e-mail contact via enquires@topotarget.com Onxeo
  More Information

No publications provided

Responsible Party: Onxeo
ClinicalTrials.gov Identifier: NCT00873119     History of Changes
Other Study ID Numbers: PXD101-CLN-17
Study First Received: March 31, 2009
Results First Received: July 1, 2014
Last Updated: July 7, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Onxeo:
Belinostat
PXD101
Carboplatin
Paclitaxel
CUP
Carcinoma of unknown primary
Occult primary

Additional relevant MeSH terms:
Carcinoma
Neoplasms, Unknown Primary
Neoplasm Metastasis
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplastic Processes
Pathologic Processes
Belinostat
Carboplatin
Paclitaxel
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Histone Deacetylase Inhibitors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on August 02, 2015